Cholesterol is central to pancreatic β-cell physiology and alterations of its homeostasis contribute to β-cell dysfunction and diabetes. Proper intracellular cholesterol levels are maintained by different mechanisms including uptake via the low-density lipoprotein receptor (LDLR). In the liver, the proprotein convertase subtilisin/kexin type 9 (PCSK9) routes the LDLR to lysosomes for degradation, thus limiting its recycling to the membrane. PCSK9 is also expressed in the pancreas and loss of function mutations of PCSK9 result in higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Aim of this study was to investigate whether PCSK9 also impacts β-cells function.
Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis / A. Marku, L. Da Dalt, A. Galli, N. Dule, P. Corsetto, A.M. Rizzo, A. Moregola, P. Uboldi, F. Bonacina, P. Marciani, M. Castagna, A.L. Catapano, G.D. Norata, C. Perego. - 136:(2022 Nov), pp. 155291.1-155291.11. [10.1016/j.metabol.2022.155291]
Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis
A. MarkuPrimo
;L. Da DaltSecondo
;A. Galli;N. Dule;P. Corsetto;A.M. Rizzo;A. Moregola;P. Uboldi;F. Bonacina;P. Marciani;M. Castagna;A.L. Catapano;G.D. Norata
Penultimo
;C. Perego
Ultimo
2022
Abstract
Cholesterol is central to pancreatic β-cell physiology and alterations of its homeostasis contribute to β-cell dysfunction and diabetes. Proper intracellular cholesterol levels are maintained by different mechanisms including uptake via the low-density lipoprotein receptor (LDLR). In the liver, the proprotein convertase subtilisin/kexin type 9 (PCSK9) routes the LDLR to lysosomes for degradation, thus limiting its recycling to the membrane. PCSK9 is also expressed in the pancreas and loss of function mutations of PCSK9 result in higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Aim of this study was to investigate whether PCSK9 also impacts β-cells function.File | Dimensione | Formato | |
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Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis.pdf
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